Pregnancy-Associated Plasma Protein A (PAPP-A) is a substance produced by the placenta during pregnancy and released into the mother’s bloodstream. This protein serves as an early indicator of how the pregnancy is progressing. Observing the concentration of this protein provides insight into the placental environment in the first trimester. Fluctuations in PAPP-A levels from the expected range can signal a need for closer monitoring as the pregnancy develops.
PAPP-A’s Role in a Healthy Pregnancy
PAPP-A’s biological function involves managing the growth factors that govern early development. PAPP-A acts as an enzyme whose primary job is to cleave Insulin-like Growth Factor Binding Proteins (IGFBPs). Specifically, it breaks down Insulin-like Growth Factor Binding Protein-4 (IGFBP-4), which normally keeps Insulin-like Growth Factors (IGFs) inactive. When IGFBP-4 is cleaved by PAPP-A, the IGFs are released, making them available to stimulate placental growth and function.
This process is fundamental for the health of the placenta and the developing fetus because IGFs promote cell proliferation and differentiation. The local regulation of these growth factors is necessary for the successful implantation of the placenta and its proper vascular development. Adequate PAPP-A activity ensures that the fetus receives the necessary nutrients and oxygen for optimal growth throughout the pregnancy.
When and How PAPP-A is Measured
PAPP-A is typically measured as part of the First Trimester Combined Screening, which is offered to pregnant individuals between the 10th and 14th week of gestation. The measurement is done through a blood draw from the mother. Timing is important because PAPP-A levels rise rapidly in the first trimester, making this period the most informative for screening.
The PAPP-A result is not assessed in isolation but is combined with two other pieces of data for a comprehensive risk assessment. These include the level of free Beta-human chorionic gonadotropin (free Beta-hCG), another placental hormone, and the Nuchal Translucency (NT) measurement. The NT is an ultrasound measurement of the fluid at the back of the baby’s neck, and the final screening calculation incorporates the mother’s age and gestational stage to estimate the risk for certain chromosomal conditions.
Interpreting Low PAPP-A Levels
A low PAPP-A result is reported in Multiples of the Median (MoM), which compares an individual’s result to the average for the same gestational age. A MoM of 1.00 is considered average, and a PAPP-A level below 0.5 MoM is commonly classified as low and requires attention. It is important to understand that a low PAPP-A level is a risk indicator and not a definitive diagnosis of any condition.
Low levels are associated with an increased statistical risk for certain fetal aneuploidies, such as Trisomy 21 (Down syndrome), Trisomy 18 (Edwards syndrome), and Trisomy 13 (Patau syndrome). When low PAPP-A is detected alongside other abnormal markers, such as an increased NT measurement or altered free Beta-hCG, the risk for these conditions is heightened. Low PAPP-A may suggest that the placenta did not establish itself optimally during the first trimester, which can affect its function later on.
This potential placental inefficiency is linked to a higher risk of several adverse pregnancy outcomes, even when the fetus is chromosomally typical. These complications include intrauterine growth restriction (IUGR) and preeclampsia, a condition characterized by high blood pressure. There is also a slightly increased risk of preterm birth and, in rare instances, stillbirth. The presence of low PAPP-A alerts the care team to the possibility of these issues, allowing for proactive measures.
Confirmatory Testing and Management
When screening results suggest an increased risk based on low PAPP-A, the next step involves offering more precise testing options. Non-Invasive Prenatal Testing (NIPT), which analyzes cell-free fetal DNA in the mother’s blood, is a common secondary screen to refine the risk assessment for aneuploidies. If the risk remains high, definitive diagnostic procedures like Chorionic Villus Sampling (CVS) or Amniocentesis may be discussed. These procedures provide a chromosomal analysis of the fetus to confirm or rule out a genetic condition.
For pregnancies with low PAPP-A but no confirmed chromosomal anomaly, management shifts to monitoring for placental-related complications. Healthcare providers often recommend a regimen of close surveillance, which may include taking low-dose aspirin daily starting around 12 weeks of gestation. This medication is thought to help improve blood flow to the placenta, potentially mitigating the risk of preeclampsia and growth restriction.
The primary management strategy involves serial ultrasounds, typically starting in the late second or early third trimester, to monitor fetal growth and placental function. These scans track the baby’s size and assess the blood flow through the umbilical cord to ensure adequate nutrient and oxygen delivery. Regular checks of the mother’s blood pressure and urine are also standard practice to detect any early signs of preeclampsia.